Contributory role of endothelium and voltage-gated potassium channels in apocynin-induced vasorelaxations

Wei Qing Han, Wing Tak Wong, Xiao Yu Tian, Yu Huang, Ling Yun Wu, Ding Liang Zhu, Ping Jin Gao

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Objective: Although apocynin, the nicotinamide adenine dinucleotide phosphate oxidase inhibitor improves vascular function in hypertension, its specificity has been questioned. The present study examined whether apocynin-induced vasorelaxations involve endothelium and/or K channels in vascular cells. Methods: Aortas from Sprague-Dawley rats were suspended in organ baths for functional studies. Changes in intracellular calcium ([Ca 2+]i) and nitric oxide ([NO]i) in rat endothelial cells were detected by fluorescence imaging. Whole-cell voltage-gated K+(Kv) currents were recorded in vascular smooth muscle cells. Results: Apocynin-induced aortic relaxations were attenuated by the absence of endothelium, endothelial nitric oxide synthase inhibitor N G-nitro-L-arginine methyl ester, or nitric oxide-dependent soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one. 4-Aminopyridine (4-AP, voltage-gated potassium channels blocker) attenuated apocynin-induced relaxations, its combined treatment with 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) did not cause further inhibition. Apocynin increased [Ca2+]i and [NO]i in endothelial cells, which were abolished by 4-AP, indicating the involvement of voltage-gated potassium channels in endothelial cells. In addition, apocynin-stimulated increase in endothelial nitric oxide synthase phosphorylation at Ser 177 depended on the presence of extracellular Ca2+. Notably, 4-AP also reduced apocynin-induced relaxations in the absence of endothelium and apocynin increased 4-AP-sensitive voltage-gated potassium channel currents in vascular smooth muscle cells. Conclusion: This study provides novel data showing that apocynin-induced relaxations of rat aortas are mediated by 4-AP-sensitive stimulation of [Ca2+]i and [NO]i increases in endothelium and by activation of voltage-gated potassium channels in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)2102-2110
Number of pages9
JournalJournal of Hypertension
Volume28
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • apocynin
  • endothelium
  • nitric oxide
  • potassium channel

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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